ABSTRACT There has been a significant rise in drugged driving, and associated traffic accidents and fatalities, in the United States over the last decade. While illegal substances account for the majority of drugged?driving cases, there are a number of prescription medications that can also impair driving ability. Most concerning are the prescription drugs which may impair driving ability after the presumed duration of therapeutic action. This phenomenon was highlighted when the FDA mandated relabeling of all hypnotic drugs containing zolpidem due to the presence of potentially impairing blood concentrations of the drug even after 8 hours; an effect that had sex-specific in its severity. This effect was exacerbated in females compared to males. Alprazolam shares many pharmacological properties with zolpidem and converging evidence suggests it may also cause prolonged psychomotor impairment beyond the proposed therapeutic duration of action. This project proposes a study enrolling an equal number of male and female healthy volunteers who will participate in six overnight sessions to evaluate if alprazolam has a negative impact on cognitive or psychomotor performance the morning after administration compared to positive and negative controls. Performance on a highly sophisticated driving simulator with high external validity will be tested before and the morning after drug administration. This randomized, double-blind study will test three therapeutic doses of alprazolam, a potentially impairing dose of zolpidem, and placebo in a mixed-factorial design?with each subject receiving all drug conditions. To evaluate if sex influences next-day alprazolam effects, sex will be analyzed as a between- subjects factor. The proposed experiment will use sensitive behavioral and analytic assessments to yield quantitative and qualitative data on previously unexplored properties of alprazolam. In light of the prevalence of drugged driving in the United States, the simulated driving data obtained from this study will have significant public health and safety implications.